Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada.
J Hum Genet. 2018 Oct;63(10):1093-1096. doi: 10.1038/s10038-018-0484-1. Epub 2018 Jul 3.
Biallelic mutations in NALCN are responsible for infantile hypotonia with psychomotor retardation and characteristic facies 1 (IHPRF1). Common features of this condition include severe neonatal-onset hypotonia and profound global developmental delay. Given the rarity of this condition, long-term natural history studies are limited. Here, we present a 9-year-old male with a homozygous nonsense mutation in NALCN (c.3910C>T, p.Arg1304X) leading to profound intellectual disability, seizures, feeding difficulties, and significant periodic breathing. Breathing irregularity was also reported in three previous patients; similar to our patient, those children demonstrated periodic breathing that was characterized by alternating apneic periods with deep, rapid breathing. As the phenotype associated with NALCN mutations continues to be delineated, attention should be given to abnormal respiratory patterns, which may be an important distinguishing feature of this condition.
NALCN 中的双等位基因突变可导致婴儿型张力减退伴运动发育迟缓及特征性面容 1 型（IHPRF1）。这种病症的常见特征包括严重的新生儿期张力减退和广泛的发育迟缓。鉴于这种病症的罕见性，长期的自然病史研究受到限制。在这里，我们介绍了一位 9 岁的男性，他在 NALCN 中存在纯合无义突变（c.3910C>T，p.Arg1304X），导致严重的智力障碍、癫痫发作、喂养困难和明显的周期性呼吸。在之前的三位患者中也有报道呼吸不规则；与我们的患者类似，这些儿童表现出周期性呼吸，其特征是呼吸暂停期与深而快速的呼吸交替。随着与 NALCN 突变相关的表型不断被描绘，应注意异常呼吸模式，这可能是这种病症的一个重要鉴别特征。
